Reduced stroke outcome in old-aged female mice maintained on a dietary vitamin B12 deficiency
Reduced stroke outcome in old-aged female mice maintained on a dietary vitamin B12 deficiency
Abstract The global population is aging and the prevalence of age-related diseases, such as stroke, is predicted to increase. A vitamin B12 deficiency (vit. B12 def.) is common in the elderly, because of changes in metabolism. Clinical studies have reported that a vit. B12 def results in worse outcome after stroke, the mechanisms through which a vit. B12 def. changes the brain requires further investigation. This study investigated the role of vit. B12 def. on stroke outcome and mechanisms using aged female mice. Eighteen month old females were put on a control or vit. B12 def. diet for four weeks, after which an ischemic stroke was induced in the sensorimotor cortex. After damage, motor function was measured and animals were euthanized and tissues were collected for analysis. Vit. B12 def. animals had increased levels of total homocysteine in plasma and liver, choline levels were also increased in the liver. Vit. B12 def. had larger damage volume in brain tissue and more apoptosis. In the cecum, changes in creatinine and methylmalonic acid were observed in vit. B12 def animals, pathway analysis showed dysfunction in B12 transport. Analysis of mitochondrial metabolomics in brain tissue showed reduced levels of metabolites involved in the TCA cycle in vit. B12 def animals. Meanwhile, pathway analysis showed significant, widespread dysfunction in phenylalanine, tyrosine, and tryptophan biosynthesis. Motor function after stroke was impaired in vit. B12 def. animals. A dietary vitamin B12 deficiency impairs motor function through increased apoptosis and changes in mitochondrial metabolism in brain tissue.
Gu Haiwei、North Sean、Weissig Volkmar、Bottiglieri Teodoro、Jadavji Nafisa M.、Kwatra Neha、Pascual Agnes S.、Jasbi Paniz、Poole Joshua
College of Health Solutions, Arizona State University||Department of Environmental Health Sciences, the Robert Stempel College of Public Health and Social Work, Florida International University||Center for Translational Science, Cellular Biology and Pharmacology Department, the Herbert Wertheim College of Medicine, Florida International UniversityCollege of Osteopathic Medicine, Midwestern University||Biomedical Sciences Program, College of Graduate StudiesBiomedical Sciences Program, College of Graduate Studies||Department of Pharmaceutical Sciences, College of Graduate Students, Midwestern UniversityCenter of Metabolomics, Institute of Metabolic Disease, Baylor Scott & White Research InstituteBiomedical Sciences Program, College of Graduate Studies||College of Veterinary Medicine, Midwestern University||Department of Neuroscience, Carleton UniversityBiomedical Sciences Program, College of Graduate Studies||College of Dental Medicine Arizona, Midwestern UniversityBiomedical Sciences Program, College of Graduate StudiesCollege of Health Solutions, Arizona State UniversityCollege of Osteopathic Medicine, Midwestern University||Biomedical Sciences Program, College of Graduate Studies
基础医学神经病学、精神病学生物化学
Gu Haiwei,North Sean,Weissig Volkmar,Bottiglieri Teodoro,Jadavji Nafisa M.,Kwatra Neha,Pascual Agnes S.,Jasbi Paniz,Poole Joshua.Reduced stroke outcome in old-aged female mice maintained on a dietary vitamin B12 deficiency[EB/OL].(2025-03-28)[2025-08-02].https://www.biorxiv.org/content/10.1101/2022.04.04.487028.点此复制
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